Editing Genetic code (section)

===Effect of mutations===
[[File:Notable mutations.svg|upright=1.75|thumb|Examples of notable [[mutation]]s that can occur in humans<ref>References for the image are found in Wikimedia Commons page at: [[Commons:File:Notable mutations.svg#References]].</ref>]]<!-- EXPANSION OF THE IMAGE WITH MORE EXAMPLES IS EXPECTED (see its discussion page)-->

During the process of [[DNA replication]], errors occasionally occur in the [[polymerization]] of the second strand. These errors, [[mutation]]s, can affect an organism's [[phenotype]], especially if they occur within the protein coding sequence of a gene. Error rates are typically 1 error in every 10–100&nbsp;million bases—due to the "[[Proofreading (biology)|proofreading]]" ability of [[DNA polymerase]]s.<ref name=griffiths2000sect2706>{{cite book |editor1-first=Anthony J. F. |display-editors=4 |editor1-last=Griffiths |editor2-first=Jeffrey H. |editor2-last=Miller |editor3-first=David T. |editor3-last=Suzuki |editor4-first=Richard C. |editor4-last=Lewontin |editor5-last=Gelbart | name-list-style = vanc |title=An Introduction to Genetic Analysis |date=2000 |isbn=978-0-7167-3520-5 |edition=7th |publisher=W. H. Freeman |location=New York |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.2706 |chapter=Spontaneous mutations }}</ref><ref name=Kunkel>{{cite journal | vauthors = Freisinger E, Grollman AP, Miller H, Kisker C | title = Lesion (in)tolerance reveals insights into DNA replication fidelity | journal = The EMBO Journal | volume = 23 | issue = 7 | pages = 1494–505 | date = Apr 2004 | pmid = 15057282 | pmc = 391067 | doi = 10.1038/sj.emboj.7600158 }}</ref>

[[Missense mutation]]s and [[nonsense mutation]]s are examples of [[point mutation]]s that  can cause genetic diseases such as [[sickle-cell disease]] and [[thalassemia]] respectively.<ref>{{Cite journal
 | pmid = 17015226
| year = 2006    
| last1 = Boillée
| first1 = S
| title = ALS: A disease of motor neurons and their nonneuronal neighbors
| journal = Neuron
| volume = 52
| issue = 1
| last2 = Vande Velde
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| last3 = Cleveland
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| pages = 39–59 
| doi = 10.1016/j.neuron.2006.09.018
| doi-access = free
}}</ref><ref name="pmid88735">{{cite journal | vauthors = Chang JC, Kan YW | title = beta 0 thalassemia, a nonsense mutation in man | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 76 | issue = 6 | pages = 2886–9 | date = Jun 1979 | pmid = 88735 | pmc = 383714 | doi = 10.1073/pnas.76.6.2886 | bibcode = 1979PNAS...76.2886C | doi-access = free }}</ref><ref name="pmid17015226">{{cite journal | vauthors = Boillée S, Vande Velde C, Cleveland DW | title = ALS: a disease of motor neurons and their nonneuronal neighbors | journal = Neuron | volume = 52 | issue = 1 | pages = 39–59 | date = Oct 2006 | pmid = 17015226 | doi = 10.1016/j.neuron.2006.09.018 | doi-access = free }}</ref> Clinically important missense mutations generally change the properties of the coded amino acid residue among basic, acidic, polar or non-polar states, whereas nonsense mutations result in a [[stop codon]].<ref name="genetics_ dictionary">{{cite book | first1 = Robert C. | last1 = King | first2 = Pamela | last2 = Mulligan | first3 = William | last3 = Stansfield | name-list-style = vanc | title = A Dictionary of Genetics|url={{google books |plainurl=y |id=5jhH0HTjEdkC}}|date=10 January 2013 | publisher = OUP USA | isbn = 978-0-19-976644-4| pages = 608 }}</ref>

Mutations that disrupt the reading frame sequence by [[indels]] ([[gene insertion|insertions]] or [[genetic deletion|deletions]]) of a non-multiple of 3 nucleotide bases are known as [[frameshift mutation]]s. These mutations usually result in a completely different translation from the original, and likely cause a [[stop codon]] to be read, which truncates the protein.<ref name="pmid8723688">{{cite journal | vauthors = Isbrandt D, Hopwood JJ, von Figura K, Peters C | title = Two novel frameshift mutations causing premature stop codons in a patient with the severe form of Maroteaux-Lamy syndrome | journal = Human Mutation | volume = 7 | issue = 4 | pages = 361–3 | date = 1996 | pmid = 8723688 | doi = 10.1002/(SICI)1098-1004(1996)7:4<361::AID-HUMU12>3.0.CO;2-0 | s2cid = 22693748 | doi-access = free }}</ref> These mutations may impair the protein's function and are thus rare in ''[[in vivo]]'' protein-coding sequences. One reason inheritance of frameshift mutations is rare is that, if the protein being translated is essential for growth under the selective pressures the organism faces, absence of a functional protein may cause death before the organism becomes viable.<ref name="pmid8444142">{{cite journal | vauthors = Crow JF | title = How much do we know about spontaneous human mutation rates? | journal = Environmental and Molecular Mutagenesis | volume = 21 | issue = 2 | pages = 122–9 | date = 1993 | pmid = 8444142 | doi = 10.1002/em.2850210205 | bibcode = 1993EnvMM..21..122C | s2cid = 32918971 }}</ref> Frameshift mutations may result in severe genetic diseases such as [[Tay–Sachs disease]].<ref name="isbn0-07-111156-5">{{cite book | last = Lewis | first = Ricki | name-list-style = vanc | title = Human Genetics: Concepts and Applications | edition = 6th | publisher = McGraw Hill | location = Boston, Mass | date = 2005| pages = 227–228| isbn = 978-0-07-111156-0 }}</ref>

Although most mutations that change protein sequences are harmful or neutral, some mutations have benefits.<ref>{{cite journal | vauthors = Sawyer SA, Parsch J, Zhang Z, Hartl DL | title = Prevalence of positive selection among nearly neutral amino acid replacements in Drosophila | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 16 | pages = 6504–10 | date = Apr 2007 | pmid = 17409186 | pmc = 1871816 | doi = 10.1073/pnas.0701572104 | bibcode = 2007PNAS..104.6504S | doi-access = free }}</ref> These mutations may enable the mutant organism to withstand particular environmental stresses better than [[wild type]] organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through [[natural selection]].<ref>{{cite journal |author=Bridges KR |title=Malaria and the Red Cell |journal=Harvard |date=2002 |url=http://sickle.bwh.harvard.edu/malaria_sickle.html |url-status=dead |archive-url=https://web.archive.org/web/20111127201806/http://sickle.bwh.harvard.edu/malaria_sickle.html |archive-date=27 November 2011 |df=dmy-all }}</ref> [[Virus]]es that use [[RNA]] as their genetic material have rapid mutation rates,<ref>{{cite journal | vauthors = Drake JW, Holland JJ | title = Mutation rates among RNA viruses | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 24 | pages = 13910–3 | date = Nov 1999 | pmid = 10570172 | pmc = 24164 | doi = 10.1073/pnas.96.24.13910 | bibcode = 1999PNAS...9613910D | doi-access = free }}</ref> which can be an advantage, since these viruses thereby evolve rapidly, and thus evade the [[immune system]] defensive responses.<ref>{{cite journal | vauthors = Holland J, Spindler K, Horodyski F, Grabau E, Nichol S, VandePol S | title = Rapid evolution of RNA genomes | journal = Science | volume = 215 | issue = 4540 | pages = 1577–85 | date = Mar 1982 | pmid = 7041255 | doi = 10.1126/science.7041255 | bibcode = 1982Sci...215.1577H }}</ref> In large populations of asexually reproducing organisms, for example, ''E. coli'', multiple beneficial mutations may co-occur. This phenomenon is called [[clonal interference]] and causes competition among the mutations.<ref>{{cite journal | vauthors = de Visser JA, Rozen DE | title = Clonal interference and the periodic selection of new beneficial mutations in Escherichia coli | journal = Genetics | volume = 172 | issue = 4 | pages = 2093–100 | date = Apr 2006 | pmid = 16489229 | pmc = 1456385 | doi = 10.1534/genetics.105.052373 }}</ref>